We presented this whole exome sequencing of smouldering multiple myeloma this year at ASH. The study is about 100 patients for which we did whole exome sequencing and targeted sequencing of one part of the cohort. The goal was to define the mutational landscape of smouldering multiple myeloma and to eventually identify markers of progression in a subgroup of patients. We had the defined mutational landscape with the main pathways, mutated pathways, which are MAP kinase and NF kappa-B, as well as the cell cycle pathway and the DNA repair pathway. We also identified a group of patients, about 50% of the patients, without mutations and a very quiet genome so it’s one of the hallmarks of smouldering multiple myeloma.
What’s interesting is that when we classified the patients based on their clinical stage, the Mayo Clinic clinical stage, we could find mutations in all the stages so they were not clustered. However, when we separated the patients between progressors and non-progressors we could clearly identify some specific mutations only in the progressor group. So it led us to develop a kind of marker where we actually identify the MAP kinase mutations and the MIC alterations that occur much more in the progressor group and in those increased risk of progression and shortened time to progression in these patients.
In terms of the clinical utility of this, of how easy it is to detect and then act on those sequences.
Yes, these are maybe preliminary data and we need to have more cohorts. But the real question behind that is about early interventions. We know now that there is a potential interest of treating these patients early on to try to cure the disease early on and before they develop overt multiple myeloma and they become symptomatic. So the real question here is that we identified these two markers, the MAP kinase pathway mutations and the MIC translocations, so do we have to treat, for example, these patients? We cannot answer yet this question but it’s definitely something that the community will have to study in a large cohort of patients and really find the risk of progression and the markers for these patients and potentially change our attitude and decision in terms of therapeutics.
Is there anything else you can think to mention? Any other details?
We are looking forward to continue this project and to be able to study a large cohort of patients and potentially have a real clinical impact of this study.